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Abstract：
The one strain many compounds (OSMAC) strategy is an effective method for activating silent gene clusters by cultivating microorganisms under various conditions. The whole genome sequence of the marine-derived strain Streptomyces globisporus SCSIO LCY30 revealed that it contains 30 biosynthetic gene clusters (BGCs). By using the OSMAC strategy, three types of secondary metabolites were activated and identified, including three angucyclines, mayamycin A (1), mayamycin B (2), and rabolemycin (3); two streptophenazines (streptophenazin O (4) and M (5)); and a macrolide dimeric dinactin (6), respectively. The biosynthetic pathways of the secondary metabolites in these three families were proposed based on the gene function prediction and structural information. The bioactivity assays showed that angucycline compounds 1-3 exhibited potent antitumor activities against 11 human cancer cell lines and antibacterial activities against a series of Gram-positive bacteria. Mayamycin (1) selectively exhibited potent cytotoxicity activity against triple-negative breast cancer (TNBC) cell lines such as MDA-MB-231, MDA-MB-468, and Bt-549, with IC50 values of 0.60-2.22 μM.
摘要：
一株多化合物（OSMAC）策略是通过在各种条件下培养微生物来激活沉默基因簇的有效方法。海洋来源的菌株球形链霉菌SCSIOLCY30的全基因组序列显示，它包含30个生物合成基因簇（BGC）。通过使用OSMAC策略，激活并鉴定了三种类型的次级代谢产物，包括三种angucyclin,MayamycinA(1),MayamycinB(2),和rabolemycin(3);两种链霉素(链霉素O(4)和M(5));和大环内酯二聚体dinactin(6),分别。根据基因功能预测和结构信息，提出了这三个家族次级代谢产物的生物合成途径。生物活性测定表明，大洋环素化合物1-3对11种人类癌细胞系具有有效的抗肿瘤活性，对一系列革兰氏阳性细菌具有抗菌活性。Mayamycin（1）对MDA-MB-231，MDA-MB-468和Bt-549等三阴性乳腺癌（TNBC）细胞系选择性地表现出有效的细胞毒性活性，IC50值为0.60-2.22μM。
